Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults. Armas Rojas NB, Lacey B, Simadibrata DM, Ross S, Varona-Pérez P, Burrett JA, et al. EClinicalMedicine. 2021 Mar 17;33:100692. 
DOI: 10.1016/j.eclinm.2020.100692. eCollection 2021 Mar.
Background The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. Methods In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. Findings After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up. Interpretation In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. Funding Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

Atxn2-CAG100-KnockIn mouse spinal cord shows progressive TDP43 pathology associated with cholesterol biosynthesis suppression. Canet-Pons J, Sen NE, Arsovic A, Almaguer-Mederos LE, Halbach MV, Key J, et al. Neurobiol Dis. 2021 Feb 10;152:105289. DOI: 10.1016/j.nbd.2021.105289. Online ahead of print.
Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy in Spinocerebellar Ataxia type 2 (SCA2). Intermediate size expansions carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression in ALS. Although ATXN2 interacts directly with RNA, and in ALS pathogenesis there is a crucial role of RNA toxicity, the affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse model with Atxn2-CAG100-KnockIn for a first definition of molecular mechanisms in spinal cord pathology. Neurophysiology of lower limbs detected sensory neuropathy rather than motor denervation. Triple immunofluorescence demonstrated cytosolic ATXN2 aggregates sequestrating TDP43 and TIA1 from the nucleus. In immunoblots, this was accompanied by elevated CASP3, RIPK1 and PQBP1 abundance. RT-qPCR showed increase of Grn, Tlr7 and Rnaset2 mRNA versus Eif5a2, Dcp2, Uhmk1 and Kif5a decrease. These SCA2 findings overlap well with known ALS features. Similar to other ataxias and dystonias, decreased mRNA levels for Unc80, Tacr1, Gnal, Ano3, Kcna2, Elovl5 and Cdr1 contrasted with Gpnmb increase. Preterminal stage tissue showed strongly activated microglia containing ATXN2 aggregates, with parallel astrogliosis. Global transcriptome profiles from stages of incipient motor deficit versus preterminal age identified molecules with progressive downregulation, where a cluster of cholesterol biosynthesis enzymes including Dhcr24, Msmo1, Idi1 and Hmgcs1 was prominent. Gas chromatography demonstrated a massive loss of crucial cholesterol precursor metabolites. Overall, the ATXN2 protein aggregation process affects diverse subcellular compartments, in particular stress granules, endoplasmic reticulum and receptor tyrosine kinase signaling. These findings identify new targets and potential biomarkers for neuroprotective therapies.

Body Mass Index Is Significantly Associated With Disease Severity in Spinocerebellar Ataxia Type 2 Patients. Almaguer-Mederos LE, Pérez-Avila I, Aguilera-Rodríguez R, Velázquez-Garcés M, Almaguer-Gotay D, Hechavarría-Pupo R, et al. Mov Disord. 2021 Feb 6. DOI: 10.1002/mds.28498. Online ahead of print.
Background Spinocerebellar ataxia type 2 is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Although weight loss has been associated with disease progression in several neurodegenerative conditions, it has been barely assessed in patients with spinocerebellar ataxia type 2. Objective The objective of this study was to test whether body mass index is altered in patients with spinocerebellar ataxia type 2 with varying expansion sizes from early to late disease stages. Methods A cross-sectional case-control study was performed, which included 222 clinically and molecularly diagnosed patients and 214 sex- and age-matched healthy individuals. ATXN2 genotypes and sex were considered as risk factors. Clinical outcomes included the body mass index, age at onset, disease duration, Scale for the Assessment and Rating of Ataxia score, disease stage, dysphagia, and progression rate. Multiple linear regression models were generated. Results Body mass index was significantly decreased in male patients, but not in female patients, relative to control subjects. In addition to sex, body mass index was significantly associated with age at onset and progression rate. Conversely, body mass index, along with repeat length in ATXN2 expanded alleles and disease duration, was associated with Scale for the Assessment and Rating of Ataxia score. In addition, body mass index, along with the age at onset and the repeat length in ATXN2 normal and expanded alleles, has a significant influence on progression rate. Conclusions Body mass index might be a useful biomarker of disease severity, particularly in male patients with spinocerebellar ataxia type 2 in the context of nutritional interventions or clinical trials assessing the efficacy of promising new drugs.

Effect of non-invasive brain stimulation on behavior and serum brain-derived neurotrophic factor and insulin-like growth factor-1 levels in autistic patients. Robinson-Agramonte MA, Michalski B, Gomez Fernández L, Vidal-Martínez B, Vera Cuesta H, Maragoto Rizo C, et al. Drug Dev Res. 2021 Mar 18. DOI: 10.1002/ddr.21808. Online ahead of print
Aberrant neural connectivity and intra-cortical inhibitory dysfunction are key features of autism. Non-invasive brain stimulation (NIBS) protocols have been proposed that modulate this aberrant plasticity. However, additional investigations are needed to evaluate the impact of this intervention on biological biomarkers of the disease. We recently demonstrated alterations in serum insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) immunoreactivity in subjects with autism compared to controls. The aim of this pilot study was to explore the change in serum levels of the neurotrophic factors BDNF and IGF-1 in patients undergoing NIBS therapy. Sixteen subjects with autism spectrum disorder (ASD) were tested 1 week before and 1 week after NIBS to determine the short-term outcome on behavior using the total score on the autism behavior checklist, autism treatment evaluation checklist, clinical global impression severity and the autism diagnostic interview. ASD subjects younger than 11 years old (n = 11) were treated with transcranial direct current stimulation (tDCS), and those 11 years and older (n = 5) were treated with repetitive transcranial magnetic stimulation (rTMS). Serum levels of BDNF and IGF-1 were evaluated by Enzyme-Linked Immuno-Sorbent Assay before and after the intervention with NIBS. A significant reduction in scores on the clinical behavioral scales was observed in patients treated with NIBS (ABC-T p = .002, CGI-S p = .008, ADI-T and ATEC-T p < .0001). There was a trend towards reduced serum BDNF levels after NIBS (p = .061), while there was no change in IGF-1 levels. These data support further studies on the potential of BDNF as a biomarker to measure the effectiveness of NIBS in autism.

Expression in Escherichia coli, purification and kinetic characterization of LAPLm, a Leishmania major M17-aminopeptidase. Aguado ME. González-Matos M, Izquierdo M, Quintana J, Field MC, González-Bacerio J. Protein Expr Purif. 2021 Mar 25;105877. 
DOI: 10.1016/j.pep.2021.105877. Online ahead of print
The Leishmania major leucyl-aminopeptidase (LAPLm), a member of the M17 family of proteases, is a potential drug target for treatment of leishmaniasis. To better characterize enzyme properties, recombinant LAPLm (rLAPLm) was expressed in Escherichia coli. A LAPLm gene was designed, codon-optimized for expression in E. coli, synthesized and cloned into the pET-15b vector. Production of rLAPLm in E. coli Lemo21(DE3), induced for 4 h at 37ºC with 400 μM IPTG and 250 μM L-rhamnose, yielded insoluble enzyme with a low proportion of soluble and active protein, only detected by an anti-His antibody-based western-blot. rLAPLm was purified in a single step by immobilized metal ion affinity chromatography. rLAPLm was obtained with a purity of ∼10 % and a volumetric yield of 2.5 μg per liter, sufficient for further characterization. The aminopeptidase exhibits optimal activity at pH 7.0 and a substrate preference for Leu-p-nitroanilide (appK_M = 30 μM, appk_cat = 14.7 s^-1). Optimal temperature is 50ºC, and the enzyme is insensitive to 4 mM Co²⁺, Mg²⁺, Ca²⁺ and Ba²⁺. However, rLAPLm was activated by Zn²⁺, Mn²⁺ and Cd²⁺ but is insensitive towards the protease inhibitors PMSF, TLCK, E-64 and pepstatin A, being inhibited by EDTA and bestatin. Bestatin is a potent, non-competitive inhibitor of the enzyme with a K_i value of 994 nM. We suggest that rLAPLm is a suitable target for inhibitor identification.

Impacts of the COVID-19 Pandemic on the Mental Health and Motor Deficits in Cuban Patients with Cerebellar Ataxias. González-Garcés Y, Dominguez-Barrios Y, Zayas-Hernández A, Sigler-Villanueva AA, Canales-Ochoa N, Hernández Oliver MO, et al. Cerebellum. 2021 Mar 25;1-8. DOI: 10.1007/s12311-021-01260-9. Online ahead of print.
Although there are no convincing evidences of detrimental effect of SARS-CoV2 infection on the cerebellum, the COVID-19 pandemic could impact the life quality of patients with cerebellar ataxias, but few studies have addressed this concern. To assess the motor and mental health changes caused by the COVID-19 pandemics in Cuban patients with cerebellar ataxias, three hundred four patients with cerebellar ataxias and 167 healthy controls were interviewed for risks of exposure to COVID-19, and the self-perception of the pandemics’ impact on the disease progression and on the mental health. All subjects underwent the Hospital Anxiety and Depression Scale. The patients reported low exposition to SARS-CoV2 infection, but one case was confirmed with a mild COVID-19. Overall, depressive and anxiety symptoms were significantly and marginally increased in patients, respectively, with higher scores in cases with severe and moderate ataxia. Positive patient’s impression of psychopathological changes was associated to increased age, age at onset, and anxiety. Sixty-seven patients had a positive self-perception of ataxia progression, which was mainly influenced by higher anxiety scores but not by the adherence to at-home exercise programs. However, the practice of physical exercise was related with lower depression and anxiety scores, but this therapeutical effect was not significantly influenced by the disease stage. We demonstrated the negative effect of the COVID-19 pandemic on the mental and motor deficits in Cuban patients with cerebellar ataxias and the positive effect of the at-home physical exercise programs on their mental well-being. These findings give rationales to develop tele-medicine approaches to minimize these health impacts and to study the long-term effects of such sequelae and accordingly define their treatments.

Immuno-toxicological evaluation of her1 cancer vaccine in non-human primates: a 6-month subcutaneous study. Mancebo Rodríguez A, Bergado Báez G, Acosta Lago E, León Goñi A, Blanco Gámez D, Fuentes Morales D, et al. Immunopharmacol Immunotoxicol. 2021 Mar 16;1-8. DOI: 10.1080/08923973.2021.1900232. Online ahead of print.
Purpose A vaccine composition based on the extracellular domain of the human epidermal growth factor receptor 1 (HER1-ECD) and the combination of VSSP (very small size proteoliposomes) and Montanide ISA 51 adjuvants when used by intramuscular route, demonstrated promising results in preclinical studies. However, in order to avoid potential adverse events due to the use of Montanide, it is proposed to modify the vaccine formulation by using VSSP (very small size proteoliposomes) adjuvant alone, and to evaluate the quality of subcutaneously induced immune response. This study aimed to assess the immunotoxicological effects of HER1 vaccine in Cercopithecus aethiops. Materials and methods Fifteen monkeys were randomized into four groups: Negative Control (Tris/NaCl, s.c.), Positive Control (200 µg HER1-ECD/VSSP/Montanide ISA-51 VG, i.m), Low Dose (200 µg HER1-ECD/VSSP/Tris NaCl, s.c.) and High Dose (800 µg HER1-ECD/VSSP/Tris NaCl, s.c). All monkeys received 7 doses and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study, and electrocardiographical and ophthalmological studies were performed. Humoral and cellular immune response and clinical pathology parameters were analyzed. Results Animal’s survival in the study was 100% (n = 15). Administration site reactions were observed in the Positive Control animals (n = 4). HER1 vaccine administered subcutaneously (High Dose Group) achieved good IgG antibody titers although lower than the Positive Control group, but with higher ability to inhibit HER1 phosphorylation. Conclusions This suggests that the alternative of eliminating the use of Montanide in the HER1 vaccine preparation and the using subcutaneous route is feasible.

Inpainting-filtering for metal artifact reduction (IMIF-MAR) in computed tomography. Rodríguez-Gallo Y, Orozco-Morales R, Pérez-Díaz M. Phys Eng Sci Med. 2021 Mar 24. DOI:10.1007/s13246-021-00990-8. Online ahead of print.
The reduction of metal artifacts remains a challenge in computed tomography because they decrease image quality, and consequently might affect the medical diagnosis. The objective of this study is to present a novel method to correct metal artifacts based solely on the CT-slices. The proposed method consists of four steps. First, metal implants in the original CT-slice are segmented using an entropy based method, producing a metal image. Second, a prior image is acquired using three transformations: Gaussian filter, Parisotto and Schoenlieb inpainting method with the Mumford-Shah image model and L0 Gradient Minimization method (L0GM). Next, based on the projections from the original CT-slice, prior image and metal image, the sinogram is corrected in the traces affected by metal in the process called normalization and denormalization. Finally, the reconstructed image is obtained by FBP and a Nonlocal Means (NLM) filtering. The efficacy of the algorithm is evaluated by comparing five image quality metrics of the images and by inspecting regions of interest (ROI). Phantom data as well as clinical datasets are included. The proposed method is compared with three established metal artifact reduction (MAR) methods. The results from a phantom and clinical dataset show the visible reduction of artifacts. The conclusion is that IMIF-MAR method can reduce streak metal artifacts effectively and avoid new artifacts around metal implants, while preserving the anatomical structures. Considering both clinical and phantom studies, the proposed MAR algorithm improves the quality of clinical images affected by metal artifacts, and could be integrated in clinical setting.

Interferon beta 1a (Rebif®) in relapsing remitting multiple sclerosis. Cardentey Sánchez R, Díaz de la Fe A, Peláez Suárez A, Grass D, Morgado Vega T, Sánchez Canal A, et al. Drug Dev Res. 2021 Feb 15. DOI: 10.1002/ddr.21798. Online ahead of print.
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that affects the central nervous system. It is the second cause of neurological disability in young adults. The exact cause of the disease remains unknown and there is no curative treatment. It is imperative to evaluate the efficacy of newest, biotechnological products modifying the disease. This study was designed to evaluate the use of interferon beta 1a (Rebif®) in patients with relapsing remitting MS treated at International Center for Neurological Restoration. Thirty-one patients with relapsing remitting MS, between 10 and 65 years of age, four males and 27 females, were treated with Rebif® three times per week during 1 year. The safety of the treatment was evaluated based on the adverse events and the efficacy based on the disability scale score, the number of attacks and the number of lesions at magnetic resonance imaging (MRI). The public clinical trial is registered in Cuba (Number B-10-030-L03). Adverse effects occurred in 75% of the cases, but they were mild. A significant reduction in the number of attacks, the disability scale score and the number of lesions at MRI were observed in patients with relapsing remitting MS treated with Rebif®. The use of interferon beta 1a showed safety and efficacy in the treatment of patients with relapsing remitting MS.

Mental health stigma and professional help-seeking attitudes a comparison between Cuba and Germany. Nohr L, Lorenzo Ruiz A, Sandoval Ferrer JE, Buhlmann U. PLoS One. 2021 Feb 11;16(2):e0246501.DOI: 10.1371/journal.pone.0246501. eCollection 2021.
Globally the burden due to mental disorders is continuously increasing. Still, professional help-seeking behavior is not fully understood. To conceive cultural determinants of help-seeking is crucial to reduce personal and social costs of (untreated) mental disorders. The current study investigates mental health stigma and help-seeking attitudes in a Cuban (n = 195) and a German (n = 165) sample. In a questionnaire survey we asked for attitudes towards mental illness and professional help-seeking in the general Cuban and German populations. The cultural context was associated with mental health stigma and professional help-seeking attitudes. Interestingly, Cuban participants reported stronger mental health stigma and more willingness to seek help. In multiple hierarchical regression analyses, community attitudes towards the mentally ill significantly predicted help-seeking attitudes, especially in the Cuban sample. Only in the German sample, more negative individual beliefs about mental illness predicted more self-stigma on help-seeking. Beyond that, cultural context moderated the association between mental health stigma and help-seeking attitudes with a stronger association between the measures in the German sample. However, gender did not predict help-seeking attitudes and self-stigma on help-seeking and no interactions between community attitudes, cultural context, and gender were found in the prediction of help-seeking attitudes. Similarities and differences between the samples are discussed in the light of the cultural contexts and peculiarities of the current samples. Concluding, implications of the current findings are reviewed.

Neurodevelopmental effects of childhood malnutrition: A neuroimaging perspective. Galler JR, Bringas-Vega ML, Tang Q, Rabinowitz AG, Imran Musa K, Chai WJ, et al. Neuroimage. 2021 Feb 5;231:117828. DOI: 10.1016/j.neuroimage.2021.117828. Online ahead of print.
Approximately one in five children worldwide suffers from childhood malnutrition and its complications, including increased susceptibility to inflammation and infectious diseases. Due to improved early interventions, most of these children now survive early malnutrition, even in low-resource settings (LRS). However, many continue to exhibit neurodevelopmental deficits, including low IQ, poor school performance, and behavioral problems over their lifetimes. Most studies have relied on neuropsychological tests, school performance, and mental health and behavioral measures. Few studies, in contrast, have assessed brain structure and function, and to date, these have mainly relied on low-cost techniques, including electroencephalography (EEG) and evoked potentials (ERP). The use of more advanced methods of neuroimaging, including magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), has been limited by cost factors and lack of availability of these technologies in developing countries, where malnutrition is nearly ubiquitous. This report summarizes the current state of knowledge and evidence gaps regarding childhood malnutrition and the study of its impact on neurodevelopment. It may help to inform the development of new strategies to improve the identification, classification, and treatment of neurodevelopmental disabilities in underserved populations at the highest risk for childhood malnutrition.

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium. Conway DI, Hovanec J, Ahrens W, Ross A, Holcatova I, Lagiou P, et al. J Epidemiol Community Health. 2021 Feb 23;jech-2020-214913. DOI: 10.1136/jech-2020-214913. Online ahead of print.
Background The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures. Methods Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman’s Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs. Results For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94). Conclusions These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

Parental Burnout Around the Globe: a 42-Country Study. Roskam I, Aguiar J, Akgun E, Arikan G, Artivia M, Avalosse H, et al. Affect Sci. 2021 Mar 18;1-22.
DOI: 10.1007/s42761-020-00028-4. Online ahead of print.
High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M_age = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress.

The Cuban Human Brain Mapping Project, a young and middle age population-based EEG, MRI, and cognition dataset. Valdés-Sosa PA, Galan-García L, Bosch-Bayard J, Bringas-Vega ML, Aubert-Vázquez EA, Rodrígues-Gil I, et al. Sci Data. 2021 Feb 5;8(1):45. DOI: 10.1038/s41597-021-00829-7.
The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 young and middle age healthy participants (31.9 ± 9.3 years, age range 18-68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion criteria included the presence of disease or brain dysfunctions. Participant data that is being shared comprises i) high-density (64-120 channels) resting-state electroencephalograms (EEG), ii) magnetic resonance images (MRI), iii) psychological tests (MMSE, WAIS-III, computerized go-no go reaction time), as well as iv,) demographic information (age, gender, education, ethnicity, handedness, and weight). The EEG data contains recordings with at least 30 minutes in duration including the following conditions: eyes closed, eyes open, hyperventilation, and subsequent recovery. The MRI consists of anatomical T1 as well as diffusion-weighted (DWI) images acquired on a 1.5 Tesla system. The dataset presented here is hosted by Synapse.org and available at https://chbmp-open.loris.ca .

VA-MENGOC-BC Vaccination Induces Serum and Mucosal Anti Neisseria gonorrhoeae Immune Responses and Reduces the Incidence of Gonorrhea. Reyes Díaz LM, Lastre González MSJB, Cuello M, Sierra-González VG, Ramos Pupo R, Lantero MI, et al. Pediatr Infect Dis J. 2021 Feb 9. DOI: 10.1097/INF.0000000000003047. Online ahead of print.
Background Overall, there are over 30 different sexually transmitted infections with Neisseria gonorrhoeae being the third most frequent with a reported 78 million cases per year. Gonococcal infection causes genital inflammation, which can be a risk factor for others sexually transmitted infections, particularly human immunodeficiency virus. Gonorrhea is a treatable disease, but recently an increase in antibiotic resistance has been of concern. There are currently no vaccines available. However, parenteral vaccination with anti N. meningitidis serogroup B vaccine has been reported to decrease the incidence of gonococcal burden in New Zealand and in Cuba despite the fact that parenteral vaccination is not deemed to induce mucosal IgA. Here we explore possible mechanisms of protection against gonococcal infection through parenteral meningococcal B vaccination. Methods Ninety-two serum, saliva and oropharyngeal swabs samples of young adults (healthy and Neisseria carriers) of the internal higher school were obtained. They have been vaccinated with VA-MENGOC-BC (MBV) during their infancy and boosted with a third dose during this study. Serum and saliva samples were analyzed by ELISA and Western blot to measured IgG and IgA antibodies against N. meningitidis and N. gonorrhoeae antigens. N. meningitidis carriers were determined by standard microbiologic test. In addition, we reviewed epidemiologic data for N. meningitidis and N. gonorrhoeae infections in Cuba. Results Epidemiologic data show the influence of MBV over gonorrhea incidence suggesting to be dependent of sexual arrival age of vaccines but not over syphilis. Laboratorial data permit the detection of 70 and 22 noncarriers and carriers of N. meningitidis, respectively. Serum anti-MBV antigens (PL) responses were boosted by a third dose and were independent of carriage stages, but saliva anti-PL IgA responses were only present and were significant induced in carriers subjects. Carriers boosted with a third dose of MBV induced similar antigonococcal and -PL saliva IgA and serum IgG responses; meanwhile, serum antigonococcal IgG was significantly lower. In saliva, at least 2 gonococcal antigens were identified by Western blot. Finally, gonococcal-specific mucosal IgA antibody responses, in addition to the serum IgG antibodies, might contributed to the reduction of the incidence of N. gonorrhoeae. We hypothesize that this might have contributed to the observed reductions of the incidence of N. gonorrhoeae. Conclusion These results suggest a mechanism for the influence of a Proteoliposome-based meningococcal BC vaccine on gonococcal incidence.

Weight loss is correlated with disease severity in Spinocerebellar ataxia type 2: a cross-sectional cohort study. Rodríguez-Gaña T, Rodríguez-Labrada R, Santana-Porbén S, Reynaldo-Cejas L, Medrano-Montero J, Canales-Ochoa N, et al. Nutr Neurosci. 2021 Mar 9;1-9. DOI: 10.1080/1028415X.2021.1895479. Online ahead of print.
Background Body weight changes occur frequently during advanced stages of Spinocerebellar Ataxia type 2 (SCA2), nevertheless limited information exists on biomarkers of nutritional status of these patients. Objective To assess changes in surrogate nutritional markers of SCA2 patients; to explore their associations with expanded CAG repeats and disease severity. Methods One-hundred-thirteen SCA2 patients and 50 healthy controls underwent a comprehensive anthropometrical and biochemical assessment protocol of the nutritional status. Neurological and genotype assessments were also performed. Results A decrease in weight, body mass index (BMI), cutaneous skinfold thickness, fat mass, arm muscle circumference, calf circumference and skeletal muscle mass was observed in SCA2 patients compared to the controls. The total/HDL cholesterol ratio was significantly reduced in patients. BMI was correlated with the age at onset. Overall, anthropometric measures were correlated with clinical markers of disease severity and were more evident in severe and moderate cases. Conclusions Using anthropometric measures in the assessment of the nutritional status of SCA2 patients might provide hints about pathophysiological mechanisms that underlie metabolic abnormalities in SCA2. Anthropometric are close related with disease severity and progression, and trigger preventive therapies aimed to ameliorate weight loss and wasting in these patients.